Ma Yuanyuan, Pan Kaisu, Shen Ling, Qu Jianhua, Han Yu, Cao Cunwei, Xue Peng
Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China.
Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
BMC Microbiol. 2025 Aug 5;25(1):480. doi: 10.1186/s12866-025-04207-w.
The human fungal pathogen Cryptococcus neoformans poses significant health risks, particularly to immunocompromised individuals, such as those with HIV/AIDS. In this study, we investigate the role of an uncharacterized protein, Taf1, in regulating ATP levels and virulence in C. neoformans. Our previous proteomic analyses confirmed the expression of Taf1, encoded by the gene CNAG_04232. We found that the deletion of the TAF1 gene resulted in the upregulation of 204 genes and the downregulation of 908 genes. Gene Ontology analysis indicated that these regulated genes are associated with metabolic and cellular processes, as well as ATP-dependent activities. Notably, the TAF1-deficient mutant exhibited impaired growth at elevated temperatures (39°C). Furthermore, in a murine model of infection, mice inoculated with the taf1Δ mutant demonstrated significantly improved survival compared to those infected with the wild-type strain, suggesting a critical role for Taf1 in virulence. Additionally, KEGG pathway analysis of RNA-Seq and metabolomics data revealed significant alterations in fatty acid biosynthesis and degradation pathways following TAF1 deletion. Collectively, these findings underscore the essential role of Taf1 in modulating cellular energy and its implications for the virulence of C. neoformans, thereby paving the way for potential therapeutic strategies targeting this pathogen.
人类真菌病原体新型隐球菌对健康构成重大风险，尤其是对免疫功能低下的个体，如感染艾滋病毒/艾滋病的患者。在本研究中，我们调查了一种未表征的蛋白质Taf1在调节新型隐球菌ATP水平和毒力方面的作用。我们之前的蛋白质组学分析证实了由基因CNAG_04232编码的Taf1的表达。我们发现，TAF1基因的缺失导致204个基因上调和908个基因下调。基因本体分析表明，这些受调控的基因与代谢和细胞过程以及ATP依赖性活动有关。值得注意的是，TAF1缺陷型突变体在高温（39°C）下生长受损。此外，在小鼠感染模型中，接种taf1Δ突变体的小鼠与感染野生型菌株的小鼠相比，存活率显著提高，这表明Taf1在毒力中起关键作用。此外，对RNA测序和代谢组学数据的KEGG通路分析显示，TAF1缺失后脂肪酸生物合成和降解途径发生了显著变化。总的来说，这些发现强调了Taf1在调节细胞能量方面的重要作用及其对新型隐球菌毒力的影响，从而为针对这种病原体的潜在治疗策略铺平了道路。
